4-Bromopyridine → tert-Butyl 4-(pyridin-4-yl)piperazine-1-carboxylate

HRID 46001

Reaction equation

HRID 46001 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[N:8]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.CC([O-])(C)C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Cl-].[Na+].O.CC([O-])=O.CC([O-])=O.[Pd+2].O>[N:5]1[CH:6]=[CH:7][C:2]([N:11]2[CH2:10][CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13][CH2:12]2)=[CH:3][CH:4]=1

Participants

10

Reactant 4

HCID 142684-BromopyridineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 57436818tert-Butyl 4-(pyridin-4-yl)piperazine-1-carboxylateYield 47%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a degassed solution of 4-bromopyridine (1 equiv.), tert-butyl piperazine-1-carboxylate (16 mmol, 1.2 equiv.) and NaOtBu (3.4 equiv.) in toluene were added Pd(OAc)2 (2 mol %) and BINAP (1 mol %) and the resulting solution was refluxed for 3 h. The reaction mixture was cooled, diluted with ethyl acetate and given water and brine washes respectively. The organic layer was dried over sodium sulfate, the solvent removed in vacuo and the crude product purified by column chromatography (silica). Yield: 47%.

Workup

  1. temperaturethe resulting solution was refluxed for 3 h
  2. temperatureThe reaction mixture was cooled
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customthe solvent removed in vacuo
  5. customthe crude product purified by column chromatography (silica)

Sources & evidence

ORD record
ord-1fb23cebb0544832ac7e9595990b2180
Source dataset
uspto-grants-2013_09
Patent number
US08541573B2

Linked notes

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